Adrenal androgen (AA) excess is a common feature of the polycystic ovarian syndrome (PCOS), although the mechanism underlying this abnormality is not known. Two to five percent of all women in the United States are affected by PCOS and AA excess affects between 40% and 60% of these patients. Notwithstanding the high frequency of this disorder, the etiology and pathogenic significance of AA excess remains unclear. The proposed study may suggest the common or underlying mechanism(s) accounting for both ovarian and AA excess, which may be basic to the development of this disorder. We hypothesize that the mechanism associating AA excess and PCOS is through excessive serine autophosphorylation, which increases both 17,20-lyase activity of the P450c17 enzyme (and consequently androgen secretion) and the degree of insulin resistance. The Aim of this proposal is to test this hypothesis by correlating adrenal 17,20-lyase activity (estimated by the response to adrenocorticotropic [ACTH] stimulation), the degree of insulin resistance (from the response to the frequently-sampled intravenous glucose tolerance test (FSIVGTT) and the level of autophosphorylation of the insulin receptor (determined in skin fibroblasts and fat) in 10 PCOS patients with and 10 without AA excess, and in 10 controls.